Inflammation
When tissue injury occurs, whether caused by bacteria,
trauma, chemicals, heat, or any other phenomenon, multiple
substances are released by the injured tissues and
cause dramatic secondary changes in the surrounding
uninjured tissues. This entire complex of tissue changes is
called inflammation.
Inflammation
Inflammation is characterized by
(1) vasodilation of the local blood vessels, with consequent
excess local blood flow;
(2) increased permeability of the capillaries, allowing leakage of
large quantities of fluid into the interstitial spaces;
(3) often clotting of the fluid in the interstitial spaces because of
increased amounts of fibrinogen and other proteins leaking from
the capillaries;
(4) migration of large numbers of granulocytes and monocytes
into the tissue; and
Mechanism of Inflammation
1. Vaso dilatation
2. Exudation - Edema
3. Emigration of cells
Macrophage and Neutrophil Responses During Inflammation
1- Tissue Macrophage Is a First Line of Defense Against Infection
2-
Neutrophil Invasion of the Inflamed Area Is a Second Line of Defense3- Second Macrophage Invasion into the Inflamed Tissue Is a Third Line of Defense
4- Increased Production of Granulocytes and Monocytes by the Bone Marrow Is a Fourth Line of Defense
Tissue Macrophage Is a First Line of Defense Against Infection
- Within minutes after inflammation begins, the macrophages
already present in the tissues, whether histiocytes in the
subcutaneous tissues, alveolar macrophages in the lungs,
microglia in the brain, or others, immediately begin their
phagocytic actions.
- When activated by the products of infection and inflammation,
the first effect is rapid enlargement of each of these cells.
- Next, many of the previously sessile macrophages break loose
from their attachments and become mobile, forming the first
line of defense against infection during the first hour or so.
Neutrophil Invasion of the Inflamed Area Is a Second Line
of Defense
- Within the first hour or so after inflammation begins, large
numbers of neutrophils begin to invade the inflamed area from
the blood.
1. Inflammatory products that are produced by inflamed tissue cause increased expression of adhesion molecules, such as selectins and intracellular adhesion molecule-1 (ICAM-1) on the surface of
endothelial cells in the capillaries and venules. These adhesion
molecules, reacting with complementary integrin molecules on the neutrophils, cause the neutrophils to stick to the capillary and venule walls in the inflamed area. This effect is called margination.
2. They also cause the intercellular attachments between the endothelial cells of the capillaries and small venules to loosen, allowing openings
large enough for neutrophils to crawl through by
diapedesis, directly from the blood into the tissue
spaces.
3. They then cause chemotaxis
of the neutrophils toward the injured tissues, as explained
earlier.
- Also within a few hours after the onset of acute, severe
inflammation, the number of neutrophils in the blood sometimes increases fourfold to fivefold—from a normal of 4000 to 5000 to 15,000 to 25,000 neutrophils per microliter. This is called neutrophilia, which means an increase in the number of
neutrophils in the blood.
- Neutrophilia is caused by products of inflammation that enter the blood stream, are transported to the bone marrow, and there act on the stored neutrophils of the marrow to mobilize these into the circulating blood. This makes even more neutrophils available to the inflamed tissue area.
- Along with the invasion of neutrophils, monocytes from the blood enter the inflamed tissue and enlarge to become
macrophages. However, the number of monocytes in the
circulating blood is low: Also, the storage pool of monocytes in the bone marrow is much less than that of neutrophils. Therefore, the buildup of macrophages in the inflamed tissue area is much slower than that of neutrophils, requiring several days to
become effective.
- Furthermore, even after invading the inflamed tissue,
monocytes are still immature cells, requiring 8 hours or more to swell to much larger sizes and develop tremendous quantities of lysosomes; only then do they acquire the full capacity of tissue macrophages for phagocytosis
- After several days to several weeks, the macrophages finally come to dominate the phagocytic cells of the inflamed area because of greatly increased bone marrow production of new monocytes.
- The fourth line of defense is greatly increased production of both granulocytes and monocytes by the bone marrow. This results from stimulation of the granulocytic and monocytic progenitor cells of the marrow.
- However, it takes 3 to 4 days before newly formed granulocytes and monocytes reach the stage of leaving the bone marrow. - If the stimulus from the inflamed tissue continues, the bone
marrow can continue to produce these cells in tremendous
quantities for months and even years, sometimes at a rate 20 to 50 times normal.
- Although more than two dozen factors have been implicated in control of the macrophage response to inflammation, five of these are believed to play dominant roles. Consist of (1) tumor necrosis factor (TNF), (2) interleukin-1 (IL-1), (3) granulocyte- monocyte colonystimulating factor (GMCSF), (4) granulocyte -colony-stimulating factor(G-CSF), and (5) monocyte-colony
stimulating factor (M-CSF). - These factors are formed by activated
macrophage cells in the inflamed tissues and in smaller quantities by
other inflamed tissue cells.
- This combination of TNF, IL-1, and colony-stimulating factors provides
a powerful feedback mechanism that
begins with tissue inflammation and proceeds to formation of large numbers of defensive white blood cells that help remove the cause of the inflammation
Eosinophils - functions
• The eosinophils normally constitute about 2 percent of all the blood leukocytes. Eosinophils are weak phagocytes, and they exhibit
chemotaxis, but in comparison with the neutrophils, it is doubtful that the eosinophils are significant in protecting against the usual types of
infection
• Count increase in Parasitic infection (hook worm, ascaris, bilharzia), and Allergic (asthma, rhinitis, drug reaction).
• Most parasites are too large to be phagocytized by eosinophils or any other phagocytic cells, alternative strategy is extracellular killing
(eosinophils attach themselves to the parasites by way of special surface molecules and release substances that kill many of the
parasites).
• For instance, in schistosomiasis, which is a parasitic infection; the
Eosinophils - functions
• Eosinophils also have a special propensity to collect in tissues in
which allergic reactions occur, such as in the peribronchial tissues of the lungs in people with asthma and in the skin after allergic skin
reactions. This is caused at least partly by the fact that many mast cells and basophils participate in allergic reactions
• Reduces inflammation caused by basophils and mast cells (they release eosinophil chemotactic factor that causes eosinophils to migrate toward the inflamed allergic tissue)
• The eosinophils are believed to detoxify some of the inflammation-inducing substances released by the mast cells and basophils and probably also to phagocytize and destroy allergen-antibody
Basophils - functions
• The basophils in the circulating blood are similar to the large tissue mast cells located immediately outside many of the capillaries in the body.
• Both mast cells and basophils liberate heparin into the blood, a substance that can prevent blood coagulation.
• The mast cells and basophils also release histamine, as well as smaller quantities of bradykinin and serotonin.
• The mast cells and basophils play an important role in some types of allergic reactions because the type of antibody that causes allergic reactions, the immunoglobulin E (IgE) type, has a special propensity to become attached to mast cells and basophils.
• Then, when the specific antigen for the specific IgE antibody
